Description du projet
Déchiffrer la détermination du sexe chez les parasites responsables du paludisme
La transmission du paludisme est causée par des parasites asexués du genre Plasmodium. Toutefois, seules les formes sexuées mâles et femelles sont capables d’infecter les moustiques, ce qui offre un créneau pour le contrôle de la maladie. Pour savoir comment les formes sexuées mâles et femelles du parasite apparaissent à partir d’un petit sous-groupe de parasites en phase sanguine, les scientifiques du projet ARISE, financé par l’UE, étudient la voie de la détermination sexuelle chez Plasmodium falciparum. Leur travail, qui implique à la fois des populations de parasites adaptés en laboratoire et de parasites sauvages, se concentre sur l’identification de déterminants moléculaires responsables de la détermination sexuelle de Plasmodium. Outre un aperçu précieux sur le processus biologique de la propagation du parasite, les résultats du projet poseront les bases de nouvelles cibles dans le traitement du paludisme.
Objectif
Malaria is caused by parasites of the genus Plasmodium. Whilst the disease is caused by asexual parasites, only sexual forms are capable of transmitting the infection to mosquitoes. Sexual forms arise from a small subset of blood-stage parasites which divert from the cycle of asexual replication and embark on a sexual developmental trajectory. Targeting the small population of parasites transmitted to mosquitoes would provide a powerful malaria control method. Although several genes have been found to have sex-specific roles, the molecular basis of the sex-determining mechanisms of Plasmodium into one or the other sex is mostly unknown.
In this proposal I will apply innovative approaches to uncover the pathway of sex-determination in P. falciparum, in both lab-adapted parasites and wild parasite populations. Specifically, I will (i) determine the earliest events in sexual dimorphism using single-cell transcriptomics (scRNAseq) in a lab-adapted P. falciparum strain (NF54); (ii) understand determinants of malaria sexual determination in wild parasites by harnessing the power of scRNAseq; (iii) identify factors that influence determination into male or female gametocytes in natural parasite populations obtained from infected carriers.
My supervisor, Dr Talman, is a leading figure in Plasmodium transcriptome analysis and sexual biology of the parasite. He has recently set up his group in Montpellier at MIGEVEC, one of the top IRD Centres in France. MIVEGEC has a unique and long history of supporting research and provides the best environment to conduct cutting-edge research in the lab as well as in challenging conditions in malaria endemic countries. Although this project represents an ambitious undertaking, I am confident my strong previous experience in malaria research and the genuine commitment to widen my field of expertise will contribute to have a major impact, providing an invaluable insight into a basic biological process essential for parasite propagation.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
13572 Marseille
France